The changes in relative amounts of hemoglobins D and A of the definitive erythroid cells during chick embryogenesis strongly resembles the switch from hemoglobin F to hemoglobin A during human development. The requlatory mechanism responsible for these changes will be examined at all levels of gene expression. Chick globin cDNA will be used to quantify the relative amounts of different globin mRNA's during development. Changes in rates of hemoglobin and globin biosynthesis will be studied biochemically. Possible regulation at the translational level will be studied by microinjection of globin mRNA into Xenopus oocytes and by cell reconstitution. Erythroid cells in culture will be manipulated to effect changes in the pattern of hemoglobin synthesis. Results from such projects will serve to further elucidate the basic mechanisms that regulate hemoglobin synthesis during development. Such information will be useful in achieving effective therapy for sickle cell disease as well as other hemoglobinopathies and blood disorders.